1. Field
This invention relates generally to glucose measurement for ongoing diabetes management. It provides a particularly useful application for implanting bioluminescent oxygen sensors within the peritoneum from which to infer glucose levels therein.
2. State of the Art
Heretofore treatment and management of diabetes has been undertaken through many and varied techniques. The approach predominantly used involves periodic pricks of the skin with a needle whereby a blood sample is obtained and tested directly to provide information about blood glucose levels. This information is then utilized as a basis from which to approximate a physiological equilibrium within the patient.
While such a direct measurement of glucose levels in blood samples from diabetes patients provides reasonably useful information about insulin levels at a given point in time, the dynamic nature of blood sugar physiology and the complexity of factors influencing blood sugar levels renders such information inadequate. Blood samples have characteristically been drawn from extremities of the body with blood sugar levels delayed from those that would normally trigger the body's more accurate natural production of insulin near the liver and kidneys in a non-diabetic patient. The glucose level in the peritoneal fluid more closely approximates the glucose level in the blood within the portal vein (which feeds the liver and kidneys), with a reduced lag time as compared to the glucose levels in the extremities such as the arms, legs and interstitial fluid. Similarly, the variables of patient food selection and amount, physical activity, insulin dosage, regimen, and protocol for a diabetes medical patient each have a dynamic impact on physiological balance within the patient's body that can change dramatically over a short period of time. If the net result of changes in these variables and dynamics results in a disequilibrium expressed as too much glucose (“hyperglycemia”), then more insulin is required, whereas too little glucose (“hypoglycemia”) requires immediate intervention to raise the glucose levels. A deleterious impact on physiology follows either such disequilibrium.
Hyperglycemia is the source of most of the long-term consequences of diabetes, such as blindness, nerve degeneration, and kidney failure. Hypoglycemia, or insulin shock, on the other hand poses the more serious short-term danger. Insulin shock can occur at any time of the day or night and can cause the patient to lose consciousness, necessitating frequent monitoring of blood glucose levels that renders the skin-prick approach impractical, particularly with young children. Even diligent patients who perform finger-sticking procedures many times each day achieve only a poor approximation of continuous monitoring. Accordingly, extensive attention has been given to the development of improved means of monitoring patient glucose levels for treatment of diabetes.
Many efforts to continuously monitor glucose levels have involved implantable electrochemical biosensors. These amperometric sensors utilize an immobilized form of the enzyme glucose oxidase to catalyze the oxidation of glucose to gluconic acid and hydrogen peroxide. Such sensors may be used to measure hydrogen peroxide resulting from the enzymatic reaction. More typically, these biosensors measure oxygen consumption.
An example of the latter, oxygen consumption, paradigm may be found in a sensor developed by David Gough and his colleagues at the Department of Bioengineering of the University of California-San Diego. This approach allows glucose and oxygen to diffuse into the enzyme-containing portion of the sensor on one side while oxygen alone diffuses through an oxygen electrode on the other side to provide contrasting information about the background concentration of oxygen.
To provide continuous measurement, biosensors are placed within the body. One method of placement is percutaneously with an indwelling needle and an attached external wire associated with a readout device. A risk of infection is associated with percutaneous biosensors. Another disadvantage of prior art percutaneously-placed biosensors is the need for recalibration to blood glucose values at least once daily and possibly more often.
Alternatively, the sensors, transmitter and battery of prior art devices have been totally implanted in the body and transmit radio signals to an external receiver. Disadvantageously, the body responds to the implant as an insult. To protect itself against a perceived invader, the body experiences a foreign body reaction by encapsulating the implant with protein, shortening the life of the total implant and adversely affecting the accuracy of information provided. Cell and proteinacious encapsulation from a foreign body reaction typically results in reduced performance from these implanted biosensors. The size of the total implant is also regarded as a problem. Further, studies of such intravascular implants portend a risk of clotting.
Studies at the University of New Mexico headed by Dr. Ebtisam Wilkins suggest that the life of sensors can be extended by periodic infusion of fresh glucose oxidase immobilized to powdered graphite in a suspension that is then pumped into a thin channel between a membrane contacting the tissues and the electrode surface, thus flushing the spent enzyme. Such periodic infusions are susceptible to all of the disadvantages attendant to invasive procedures.
Material prior art further includes U.S. Pat. No. 4,657,736 to Marsoner, et al. entitled “Sensor element for determining the oxygen content and a method of preparing the same;” and U.S. Pat. No. 5,030,420 to Bacon, et al. entitled “Apparatus for oxygen determination.” Marsoner teaches use of a sensor containing any of various fluorescent indicator substances solubilized in generally homogeneous distribution throughout a polymerized silicone polymer carrier material. Such fluorescent indicator substances tend to be toxic to a patient or other biological hosts. Disadvantageously, when such fluorescent indicator substances are dissolved homogeneously throughout a carrier, a greater exposure of the patient or other biological host to the toxic fluorescent substances is likely to result. Bacon similarly teaches fluorescing complexes immobilized and isolated throughout an insoluble matrix such as light-transmissive silicone rubber.
There remains a need for a sensor apparatus wherein a fluorescing indicator substance is encapsulated within a surrounding barrier rather than dispersed homogeneously throughout such barrier. The need would be beneficially addressed at least in part by provision of an implantable sensor wherein an indicator substance capable of fluorescing is encapsulated within an oxygen permeable silicone polymer carrier material.
A need exists for a sensor suitable for location in the vicinity of the peritoneum as a part of a system and method for inferring glucose levels within the peritoneum. This need would be addressed by location of a sensor within the peritoneum, whether other portions of the system associated with the sensor, such as light source, photoreceptors, batteries and CPU, are located outside of the body or embedded within the body. Such a sensor would beneficially be susceptible to periodic revitalization, preferably less invasively or noninvasively.
A further need exists for a method of infusing insulin into the vicinity of the peritoneum in response to inferences of glucose levels within the peritoneum suggestive of the onset of a hyperglycemic condition. Such a means would desirably allow for the subject patient to directly respond by affecting the timing and nature of such insulin infusion relative to prevailing conditions or would alternatively allow for a third party or automated response that may in one alternative embodiment be remotely actuated.